Mast cells and basophils, which are activated by immunoglobulin E (IgE) and allergen, play a prominent role in anaphylaxis. However, they express at least three types of IgE receptors: the high affinity IgE receptor (FcepsilonRI), and the two low affinity IgG receptors (FcgammaRII and FcgammaRIII) also capable of binding IgE. We have generated mice deficient with a disrupted FcepsilonRI alpha chain gene. This defect results in complete suppression of the cell surface expression of FcepsilonRI. These mice appear normal and express a normal number of mast cells, but they are resistant to cutaneous and systemic anaphylaxis. These data demonstrate that FcepsilonRI is necessary for the initiation of IgE-dependent anaphylactic reactions. We are now analyzing the response of our FcepsilonRI deficient mice in active anaphylaxis experiments. In humans, IgE and FcepsilonRI present on eosinophils have also been shown to play a prominent role in the defense against parasites. In experimantal infections with Schistosoma mansoni, Nippostrongylus brasiliensis and Heligmosomoides polygyrus, no difference was observed between the FcepsilonRI deficient mice and normal animals suggesting that in mice, anti-helminthic immunity was not mediated through FcepsilonRI. We have generated mice with a disrupted FcepsilonRI beta chain gene. Those animals are also resistant to anaphylaxis. In humans, conflicting data have been correlating atopy with mutations in the beta gene and its maternal imprinting. We have used mice carrying one copy of the disrupted allele inherited from either parents to show that, at least in rodents, there was no imprinting of the beta gene. The beta chain also associates with FcgammaRIII and we are investigating its contribution in the FcgammaRIII-mediated cell activation. We have also obtained mice with both alpha and beta disrupted.